Biomimetic liposomal co-delivery of quercetin and carnosine for enhanced transdermal penetration and NRF2/HES1-mediated antioxidant photoprotection.

Xiuyuan Xia, Zhenghan Zhang, Yizhen Wang, Chen Chen, Yaqi Wang, Yanting Luo, Ying Gao, Weiyong Hong, Chuanpeng Ren

Department of Pharmacy, Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital), School of Medicine, Taizhou University, #581 East Shifu Avenue, Taizhou, 318000, PR China. · pubmed

Paper

Abstract

Quercetin and carnosine, natural antioxidants with anti-aging and photoprotective potential, face therapeutic limitations due to poor skin permeability. We engineered EV-QuerCar, a liposomal-based nanoparticles (LPNs) system co-encapsulating both compounds, to enhance transdermal delivery and evaluate its structural and functional efficacy. EV-QuerCar was prepared biomimetically using thermophilic bacterial lipids via ultracentrifugation, thin-film hydration, and high-pressure homogenization. Physicochemical properties, transdermal penetration, cellular uptake, and cytotoxicity were tested in vitro. Molecular docking and qPCR assessed pathway targeting. EV-QuerCar exhibited uniform size (94.70 ± 0.71 nm), high encapsulation efficiency (90.07%), sustained release, and 3.21-fold enhanced transdermal absorption compared to free compounds. Cellular uptake in fibroblasts increased time-dependently (up to 5.48-fold at 4 h). Molecular docking and qPCR confirmed interactions with NRF2 and HES1 targets, significantly upregulating their mRNA levels (2.29- and 3.35-fold, respectively) in UV-exposed human fibroblasts. EV-QuerCar improves skin permeability and antioxidant efficacy, highlighting its cosmeceutical promise.

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Research summary

The paper claims that the engineered liposomal system EV-QuerCar significantly enhances transdermal delivery and antioxidant efficacy of quercetin and carnosine, targeting NRF2 and HES1 pathways. This research is relevant as it explores innovative methods to improve skin antioxidant defenses, which may contribute to mitigating age-related skin damage and promoting longevity.

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